Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children.

ABSTRACT:

Background and objective

Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by insufficient levels of survival motor neuron (SMN) protein. Risdiplam (Evrysdi^TM) increases SMN protein and is approved for the treatment of SMA. Risdiplam has high oral bioavailability and is primarily eliminated through hepatic metabolism by flavin-containing monooxygenase3 (FMO3) and cytochrome P450 (CYP) 3A, by 75% and 20%, respectively. While the FMO3 ontogeny is critical input data for the prediction of risdiplam pharmacokinetics (PK) in children, it was mostly studied in vitro, and robust in vivo FMO3 ontogeny is currently lacking. We derived in vivo FMO3 ontogeny by mechanistic population PK modelling of risdiplam and investigated its impact on drug-drug intera

SUBMITTER: Cleary Y 

PROVIDER: S-EPMC10256639 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature